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      T-lymphocyte maturation abnormalities in uninfected newborns and children with vertical exposure to HIV.

      Blood
      Adult, Age Factors, Antigens, CD4, blood, Antigens, Surface, CD8-Positive T-Lymphocytes, immunology, secretion, Cell Differentiation, Child, Child, Preschool, Cohort Studies, Female, HIV Envelope Protein gp160, pharmacology, HIV Infections, transmission, HIV Seropositivity, Humans, Immunity, Cellular, Infant, Newborn, Infectious Disease Transmission, Vertical, Interferon-gamma, Interleukin-7, Lymphocyte Activation, drug effects, Male, Mitogens, Mothers, T-Lymphocytes, pathology

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          Abstract

          Cell-mediated immunity and T-lymphocyte maturation are impaired in HIV-infected children. These abnormalities would be detected in HIV-uninfected offspring of HIV women (seroreverters [SR]) if HIV or its soluble proteins could cross the placental barrier. Immunophenotypic analyses were performed in 20 healthy HIV-uninfected newborns of HIV-infected mothers (SR), and in 14 healthy newborns of HIV-negative women (UC). The same analyses were performed in 3 groups of older children: SR (n = 41); UC (n = 15); and HIV-infected children (n = 25). Antigen-specific cells were evaluated with ELISpot and fluorimetric analyses; IL-7 serum concentration was measured by enzyme-linked immunosorbent assay (ELISA). Results showed that in SR newborns: (1) the CD4/CD8 ratio was reduced, (2) CD4(+) and CD8(+) naive T-cell percentages were decreased, (3) percentage of activated CD8(+) T cells was increased, and (4) percentages of CD3(+)/4(-)/8(-) (DN) and DN/25(-)/44(+) were augmented. These abnormalities were partially retained in older SR children. CD4(+) and CD8(+) HIV-specific cells were detected in a portion of newborn SRs but not in older SRs. Serum IL-7 was augmented both in newborn and older SRs. Cell-mediated immunity and T-cell maturation are altered even in HIV-uninfected newborns of HIV-infected mothers; these abnormalities persist over time. The biologic significance of these observations and potential subsequent clinical events should be investigated in larger cohorts of seroreverters. (Blood. 2000;96:3866-3871)

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